The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01719380




Registration number
NCT01719380
Ethics application status
Date submitted
30/10/2012
Date registered
1/11/2012

Titles & IDs
Public title
Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in BRAF Mutant Metastatic Colorectal Cancer
Scientific title
A Phase Ib/II Multi-center, Open-label, Dose Escalation Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in Patients With BRAF Mutant Metastatic Colorectal Cancer
Secondary ID [1] 0 0
C4221002
Secondary ID [2] 0 0
CLGX818X2103
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: LGX818 + cetuximab -

Experimental: LGX818 + BYL719 + cetuximab -

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b: Number of Participants With Incidence of Dose Limiting Toxicities (DLTs): Cycle 1
Timepoint [1] 0 0
Cycle 1: Day 1 to Day 28
Primary outcome [2] 0 0
Phase 2: Progression Free Survival (PFS)
Timepoint [2] 0 0
From the date of randomization until the first documentation of disease progression or death due to any cause, censored date, whichever occurred first (maximum up to 43 months)
Secondary outcome [1] 0 0
Number of Participants With Treatment - Emergent Adverse Events of Grade 3 or 4 Severity Based on National Cancer Institute of Common Terminology Criteria (NCI-CTCAE), Version 4.0
Timepoint [1] 0 0
From screening up to 30 days after the last dose of study treatment (for a maximum duration of 43 months, approximately)
Secondary outcome [2] 0 0
Apparent Total Plasma Clearance (CL/F) of LGX818 (Encorafenib)
Timepoint [2] 0 0
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [3] 0 0
Apparent Total Plasma Clearance at Steady State (CL/F, ss) of LGX818 (Encorafenib)
Timepoint [3] 0 0
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [4] 0 0
Apparent Total Plasma Clearance (CL/F) of BYL719 (Alpelisib)
Timepoint [4] 0 0
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [5] 0 0
Apparent Total Plasma Clearance at Steady State (CL/F, ss) of BYL719 (Alpelisib)
Timepoint [5] 0 0
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [6] 0 0
Apparent Terminal Volume of Distribution (Vz/F) of LGX818 (Encorafenib)
Timepoint [6] 0 0
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [7] 0 0
Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of LGX818 (Encorafenib)
Timepoint [7] 0 0
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [8] 0 0
Apparent Terminal Volume of Distribution (Vz/F) of BYL719 (Alpelisib)
Timepoint [8] 0 0
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [9] 0 0
Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of BYL719 (Alpelisib)
Timepoint [9] 0 0
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [10] 0 0
Time to Reach Maximum Observed Plasma Concentration (Tmax) of LGX818 (Encorafenib)
Timepoint [10] 0 0
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [11] 0 0
Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of LGX818 (Encorafenib)
Timepoint [11] 0 0
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [12] 0 0
Time to Reach Maximum Observed Plasma Concentration (Tmax) of BYL719 (Alpelisib)
Timepoint [12] 0 0
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [13] 0 0
Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of BYL719 (Alpelisib)
Timepoint [13] 0 0
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [14] 0 0
Time of Last Observed Plasma Concentration (T-last) of LGX818 (Encorafenib)
Timepoint [14] 0 0
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [15] 0 0
Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of LGX818 (Encorafenib)
Timepoint [15] 0 0
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [16] 0 0
Time of Last Observed Plasma Concentration (T-last) of BYL719 (Alpelisib)
Timepoint [16] 0 0
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [17] 0 0
Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of BYL719 (Alpelisib)
Timepoint [17] 0 0
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [18] 0 0
Plasma Trough Concentration at Steady State (Ctrough, ss) of LGX818 (Encorafenib)
Timepoint [18] 0 0
Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [19] 0 0
Plasma Trough Concentration at Steady State (Ctrough, ss) of BYL719 (Alpelisib)
Timepoint [19] 0 0
Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Secondary outcome [20] 0 0
Overall Survival (OS)
Timepoint [20] 0 0
From the date of randomization or date of start of treatment to the date of death due to any cause or data censoring date, whichever occurred first (up to 43 months)
Secondary outcome [21] 0 0
Overall Response Rate (ORR)
Timepoint [21] 0 0
From date of randomization or date of start of treatment until date of first documentation of PD or death due to any cause (maximum up to 43 months)
Secondary outcome [22] 0 0
Duration of Response (DOR)
Timepoint [22] 0 0
From the first documentation of OR (confirmed CR or PR) to first documentation of PD/death due to any cause or censoring date, whichever occurred first (up to 43 months)
Secondary outcome [23] 0 0
Time to Response (TTR)
Timepoint [23] 0 0
From the date of randomization or date of start of treatment until first documented response (CR or PR) or data censoring date, whichever occurred first (maximum up to 43 months)
Secondary outcome [24] 0 0
Phase 1b: Progression Free Survival (PFS)
Timepoint [24] 0 0
From date of start of treatment to the date of event defined as the first documented progression or death due to any cause, censored date, whichever occurred first (maximum up to 43 months)
Secondary outcome [25] 0 0
Phase 2: Number of Participants With Any Variant in Gene Status at Baseline
Timepoint [25] 0 0
Baseline (Day 1)

Eligibility
Key inclusion criteria
* Metastatic colorectal cancer
* Progression after at least one prior standard of care regimen or be intolerant to irinotecan-based regimens
* Life expectancy = 3 months
* ECOG performance status = 2
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Symptomatic or untreated leptomeningeal disease
* Symptomatic brain metastasis
* Patients with clinically manifested diabetes
* Acute or chronic pancreatitis
* Clinically significant cardiac disease

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Utah
Country [8] 0 0
Belgium
State/province [8] 0 0
Vlaams Brabant
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
France
State/province [11] 0 0
Montpellier
Country [12] 0 0
France
State/province [12] 0 0
Toulouse
Country [13] 0 0
Germany
State/province [13] 0 0
Nordrhein-westfalen
Country [14] 0 0
Germany
State/province [14] 0 0
Essen
Country [15] 0 0
Italy
State/province [15] 0 0
Modena
Country [16] 0 0
Japan
State/province [16] 0 0
Chiba
Country [17] 0 0
Japan
State/province [17] 0 0
Tokyo
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul Teugbyeolsi
Country [19] 0 0
Netherlands
State/province [19] 0 0
Noord-holland
Country [20] 0 0
Netherlands
State/province [20] 0 0
Zuid-holland
Country [21] 0 0
Netherlands
State/province [21] 0 0
Utrecht
Country [22] 0 0
Norway
State/province [22] 0 0
Oslo
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Spain
State/province [25] 0 0
Sevilla

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.